The overall objective of this proposed research is to establish a basic understanding of the metabolism of intermediates involved in melanin synthesis and to then use this knowledge to evaluate the possibility of biochemically determining the tissue site of metastatic melanoma through the analysis of tumor related metabolic excretion products found in the urine. Primary to these objectives is the establishment of organ specific blood borne tumor metastases in the hamster melanoma model as has been done with the B-16 mouse melanoma model. There are three hypotheses relating to the origin of these compounds which requires evaluation; (1) these intermediary metabolites arise from alterations in the primary synthesis of the melanin polymer, and thus involve alterations at the molecular level; (2) there may be genetic differences amongst the melanoma cells, "polyclonism", which through a process of tumor progression, express these biochemical differences in terms of their production of intermediate metabolites and (3) melanoma cells may be identical but that variation in excretion patterns arise either from individual differences in the host organism, or in the nature of the metastatic sites involved. The questions we propose to answer here require (1) the hamster melanoma model system which appropriately imitates the biochemistry of human melanoma; (2) cell culturing for developing tissue specific metastic tumor clones and (3) a special ion exchange liquid column chromatography method developed at this institution for detection of pigmentary metabolites.